title: Activation of mammalian target of rapamycin pathway confers adverse outcome in nonsmall cell lung carcinoma.
abstract: BACKGROUND
  Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC).
  
  
  METHODS
  The protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis.
  
  
  RESULTS
  Compared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage.
  
  
  CONCLUSIONS
  This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC.
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Bojiang
authors.initials: B
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.forename: Shangfu
authors.initials: S
authors.lastname: Zhang
authors.forename: Lunxu
authors.initials: L
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Xianming
authors.initials: X
authors.lastname: Mo
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D010770:Phosphotransferases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases